Abdollah Jafarzadeh

Background: Macrophages are essential immune cells during Leishmania infection, as their polarization toward M1/M2 phenotypes determines disease outcome. This study aimed to investigate the modulatory effects of leptin, alone and in combination with glucantime, on macrophage polarization in Leishmania tropica infection. Methods: Human THP-1-derived macrophages infected with L. tropica were treated with leptin (5 or 10 ng/ml), glucantime (100 or 200 μg/ml), or their combinations. The cytotoxic effects, parasite survival, reactive oxygen species (ROS), nitric oxide (NO) generation, and expression of M1/M2 acrophage-related parameters were evaluated using standard methods. Results: Both leptin doses significantly increased the expression of M1-associated markers (CD86, iNOS, SOCS3, miR-155) and pro-inflammatory cytokines (TNF-α, IL-12, IFN-γ) while decreasing M2-associated markers (CD206, ARG1, SOCS1, miR-146a) and anti-inflammatory cytokines (IL-4, IL-10, TGF-β). The leptin-glucantime combinations showed synergistic effects, shifting macrophage polarization toward the M1 phenotype more than either treatment alone. In particular, the combination of 10 ng/ml leptin with 100 μg/ml glucantime completely eliminated intracellular amastigotes and showed a superior selectivity index (17.66) compared to mono-treatment (leptin: 7.88; glucantime: 6.87). Conclusions: The findings indicate that leptin enhances the efficacy of glucantime against L. tropica by promoting M1 macrophage polarization. This presents a potential therapeutic approach that may lower conventional drug doses and associated toxicity while preserving or even improving treatment outcomes. Graphical

Staphylococcus aureus (S. aureus) is a common cause of nosocomial infections, posing substantial public health challenges. The current study employed a synthesized zingerone-potassium-doped ZnO (Zin-K-ZnO) nanoparticles (NPs) against the growth and biofilm formation by S. aureus. A real-time PCR was used for assessment of the expression of antibiotic resistance and virulence factor (mecA and spA, respectively) in S. aureus under treatment with the NPs compared to control. 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay was used to determine the cytotoxicity of the NPs based on the survival percentage of HCT-116 cells cultured with NPs of the concentration obtained for MIC. Structure analyses revealed that the NPs exhibited an approximately spherical morphology, with an average diameter of 37 nm. Antibacterial activity assessment demonstrated dose-dependent inhibition of S. aureus growth by the NPs. The minimum inhibitory concentration (MIC) of Zin-K-ZnO NPs (9.5 mM) was significantly lower than the value for zingerone (56 mM). Furthermore, Zin-K-ZnO NPs at the concentration of 64-1024 mg/mL prevented S. aureus biofilm formation by 19.9-81.0 ± 4.7%, which was significantly more effective compared to zingerone. Additionally, the NPs led to a substantial decrease in the expression of spA and mecA genes in S. aureus. MTT result revealed that NPs with the concentration of 9.5 mM had low cytotoxicity (92% cell viability) on HCT-116 cells. The results highlighted the strong antibacterial properties exhibited by both zingerone and Zin-K-ZnO NPs against S. aureus growth and biofilm formation.

MicroRNAs (miRNAs) are key regulators of gene expression that bind to the 3′-untranslated region (3′-UTR) of target mRNAs, modulating protein expression and influencing cancer progression. Among these, microRNA-152 (miR-152) is frequently downregulated in diverse malignancies—including breast, endometrial, gastrointestinal, and hematologic cancers—primarily due to promoter hypermethylation. This epigenetic silencing, mediated by DNMT1, is compounded by competitive sponging from long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), forming intricate regulatory networks. Functionally, miR-152 acts as a tumor suppressor by targeting oncogenic pathways such as PI3K/AKT/mTOR, EMT drivers, and chemoresistance mediators. However, its role is context-dependent, exhibiting dual oncogenic and suppressive effects in prostate cancer and certain leukemias. Therapeutically, restoring miR-152 expression via mimics, demethylating agents, or nanocarrier-based delivery systems shows promise in preclinical studies for reversing chemoresistance and inhibiting metastasis. This review synthesizes miR-152’s upstream regulators, downstream targets, and clinical potential, offering a roadmap for its exploitation in precision oncology.

Prolactin (PRL) is secreted by various cells in the anterior pituitary gland, mammary glands, placenta, uterus, ovaries, testes, skin, adipose tissue, endothelial cells, immune system, and central nervous system. The expression and secretion of PRL are influenced by several factors such as suckling, thyrotropin‐releasing hormone (TRH), cytokines, dopamine, estrogen, and vasoactive intestinal polypeptide. It operates through a complex receptor, which is expressed in mammary gland cells, pancreatic beta cells, adipocytes, and immune cells. PRL is essential for various physiological functions, in particular milk production, breast development, metabolism, and immune regulation. Serum PRL levels fluctuate daily and can be affected by exercise, diet, and stress. Hyperprolactinemia is linked to autoimmune diseases and viral infections. In viral infections such as HIV, HCMV, HCV, and COVID‐19, PRL levels are often increased, which may influence the immune responses. PRL can modulate the activity of various immune cells, including T cells, B cells, natural killer cells, and macrophages, mounting an effective immune response against viral infections. Moreover, PRL influences the production of cytokines that mediate and regulate immunity and inflammation. PRL stimulates B cells to produce antivirus antibodies that are essential for neutralizing viruses and preventing their spread within the body. PRL levels, varying by sex and life stage, may affect immune responses and susceptibility to viral infections. Moreover, overexpression of PRL was indicated in various autoimmune diseases. Overall, PRL is a complex hormone with significant implications for endocrine function, immune regulation, and immune responses to viral infections, highlighting the need for further research into its diverse roles in health and disease. This review summarizes current knowledge of the immunomodulatory effects of PRL in human viral infections and possibly its contribution to the development of autoimmune diseases.

Apelin, a bioactive peptide that serves as an endogenous ligand for the apelin receptor (APJ), is overexpressed in various types of cancers and contributes to cancer cell proliferation, viability, migration, angiogenesis, and metastasis, as well as immune deviation. Noncoding RNAs (ncRNAs) regulate gene expression, and there is growing evidence suggesting a bidirectional crosstalk between ncRNAs (including long noncoding RNAs [lncRNAs], circular RNAs [circRNAs], and microRNAs [miRNAs]) and apelin in cancers. Certain miRNAs can directly target the apelin and inhibit its expression, thereby suppressing tumor growth. It has been indicated that miR‐224, miR‐195/miR‐195‐5p, miR‐204‐5p, miR‐631, miR‐4286, miR‐637, miR‐4493, and miR‐214‐3p target apelin mRNA and influence its expression in prostate cancer, lung cancer, esophageal cancer, chondrosarcoma, melanoma, gastric cancer, glioma, and hepatocellular carcinoma (HCC), respectively. Moreover, circ‐NOTCH1, circ‐ZNF264, and lncRNA BACE1‐AS upregulate apelin expression in gastric cancer, glioma, and HCC, respectively. On the other hand, apelin has been shown to regulate the expression of certain ncRNAs to affect tumorigenesis. It was revealed that apelin affects the expression of circ_0000004/miR‐1303, miR‐15a‐5p, and miR‐106a‐5p in osteosarcoma, lung cancer, and prostate cancer, respectively. This review explains a bidirectional interplay between ncRNAs and apelin in cancers to provide insights concerning the molecular mechanisms underlying this crosstalk and potential implications for cancer therapy.